Otitis media leads to enormous morbidity and to direct annual healthcare costs estimated to be $3 billion in the U.S. Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death in the U.S. Bacterial infection in COPD causes substantial morbidity and mortality. Two of the three most common bacterial pathogens to cause otitis media and respiratory tract infections in COPD are non-typeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis. The development of vaccines to prevent otitis media and respiratory tract infections in adults with COPD would have important impact in reducing mortality, preventing morbidity and reducing healthcare costs in these settings. This program project proposes studies which will elucidate the immune response to specific antigens of NTHI and M. catarrhalis. Our hypothesis is that the pattern of respiratory tract infections due to NTHI and M. catarrhalis in children and adults depends on the immune response to specific surface antigens of the organisms. The aims of the project will be accomplished through the efforts of a multi-disciplinary research team which will collaborate to carry out three interrelated projects. Project 1 will characterized the role of human T cell responses to protein P6, a promising vaccine antigen will be determined through studies with carefully defined samples from humans. Project 3 will focus on antigenic characterization of the lipooligosaccharide (LOS) of M. catarrhalis, the role of NOS as an adhesin and the human immune response to determinants on the LOS molecule. An Administrative/Statistical Core will coordinate the program and provide statistical expertise to each of the projects. Since NTHI and M. catarrhalis are exclusively human pathogens, a strong emphasis is placed on elucidation of the human immune response. The proposed studies will advance the field of vaccine development to prevent otitis media and respiratory tract infections in COPD.